Amantadine



Better Known as: Symmetrel

 * Marketed By: Endo Pharmaceuticals
 * Major Indication: Influenza Infection
 * Drug Class: M2 Proton Channel Inhibitor
 * Date of FDA Approval (Patent Expiration): 1966 (1986)
 * 1994 Sales: N/A
 * Importance: One of the the first treatments approved by the FDA and the first approved for treatment of Influenza Infections. Nearly 100% of influenza viruses had developed resistance to rimantadine, and it is no longer recommended as a treatment for the flu. Interestingly, in 1969 it was also discovered that Amantadine helped reduce the symptoms of Parkinson's Disease.
 * See Pharmaceutical Drugs for more information about other drugs and disorders.

Mechanism of Action
The Influenza A Virus viral envelope is dotted with various ion channels including M2 Proton Channels. The M2 protein plays a critical role in the life cycle of the Influenza virus. It enables hydrogen ions to enter the virion form the endosome. The result of this is a more acidic environment within the virus, causing dissociation of the viral matrix protein M1 from the ribonucleoprotein RNP. Dissociation of the viral matrix protein is a crucial step in uncoating of the virus and exposing its contents to the cytoplasm of the host cell, allowing the virus to hijack the cellular machinery to replicate. Amantadine binds to the pore formed by the M2 protein, utilizing Val 27, Ala 30 and Ser 31 in each M2 protein chain, effectively disabling the protein from transferring protons into the viral particle.